3-49329308-G-C

Position:

• chr3-49329308-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003363.4(USP4):​c.230-1492C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,042 control chromosomes in the GnomAD database, including 2,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2956 hom., cov: 32)
• Consequence: USP4 NM_003363.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

USP4 (HGNC:12627): (ubiquitin specific peptidase 4) The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP4	NM_003363.4	c.230-1492C>G		intron_variant		ENST00000265560.9	NP_003354.2
USP4	NM_001251877.2	c.230-1492C>G		intron_variant			NP_001238806.1
USP4	NM_199443.3	c.230-1492C>G		intron_variant			NP_955475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP4	ENST00000265560.9	c.230-1492C>G		intron_variant		1	NM_003363.4	ENSP00000265560	A1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28501 AN: 151924 Hom.: 2955 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.188 AC: 28514 AN: 152042 Hom.: 2956 Cov.: 32 AF XY: 0.186 AC XY: 13833 AN XY: 74296

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0443

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.191

Alfa AF: 0.0565 Hom.: 69

Bravo AF: 0.184

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9863142; hg19: chr3-49366741;